Antibody Secreting Cells and Dengue Virus Infections

Antibody producing by B cells is important in defending pathogens in a host even though it takes times to develop. However, the educated B cells, mainly reside in bone marrow (BM), possess a capacity of recalled activity and can have robust antibody production in a short time upon encountering the same pathogens to timely contain and eliminate the pathogens through neutralizing capacity. Although the scenarios are true for majority of pathogens, a few of pathogens do deviate from the dogma. One of such pathogens is dengue virus (DENV), a causative agent of dengue. Bone marrow suppression is a salient clinical finding in acute dengue patients and people who are previous infected by DENV can be experienced re-infection. Despite it has been reported that the antibody is short-lived in DENV infected individuals, and yet the status of antibody secreting cells in acute infected dengue subjects remains largely unexplored. Previously, we found that BM suppression could be a consequence of BM cells directly infected by DENV since BM cells were found to be permissive to DENV infection and DENV virus could be recovered from DENV infected CD133+ stem cells. Here, we analyzed the status of T and B cells in NS1- or NS1+ BM by FACS. Results showed that the status of T cells, either memory CD4 or CD8, did not alter significantly between NS1- and NS1+ BMs. However, the naïve and resting memory B cells were decreased, while tissue-like memory did increase in NS1+ BMs compared to NS1- BMs. Further analysis demonstrated that antibody secreting cells (ASCs) were significantly decreased in NS1+ BMs compared to NS1- BMs, in contrast, the activated memory B cells were no different. Functional analysis revealed that plasma cells within ASCs were significantly reduced in NS1+ BM, but the plasmablast cells were significantly increased. The loss of plasma cells also resulted in the loss of IgG+IgM- and IgG+IgM+ populations. The cumulative data suggested that the levels of plasma cells and plasmablast cells in NS1+ BM were significantly decreased. The results may suggest why measurement of the antibody for previously DENV infected subjects upon re-infection required two specimens, and could pave a new avenue to fine-tuning the efficacy of current dengue vaccine.